Description: (Applicant's Description) The Structural Biology Program is a new addition to the Cancer Center and resulted from the natural convergence of. 1 The necessity for structural information in cancer research; 2 The recruitment of an expert group of structural biologists and establishment of a Center for Structural Biology at the University of Virginia and; 3 The cancer-focus of many of the scientific interests of these investigators, including the multi-drug resistance P-glycoprotein, the Ras oncogene, the small GTPase, RhoA. and the phosphotyrosine-binding adapter protein, Shc. The overall goal of the Program is to integrate, through interdisciplinary collaborations, structural with functional studies of oncogenesis, metastasis and, ultimately, cancer therapy. Expertise and methodologies available include X-ray crystallography, NMR and EPR spectroscopy, atomic force and cryo-atomic force microscopy, total internal reflectance fluorescence microscopy, laser scanning confocal microscopy, X-ray mapping, energy filtered scanning electron microscopy and electron probe X-ray microanalysis. In the short time since the Program was established (May 1998) we made significant advances in high resolution structure determination of cancer related proteins (small GTPase-FAK), and initiated pilot projects (multi-drug resistance glycoprotein P). The Program also disseminates the value and use of structural methods through a seminar series featuring internationally renowned structural biologists.